Treatment of pre-school children under 6 years of age for schistosomiasis: safety, efficacy and acceptability of praziquantel

BackgroundThe World Health Organization (WHO) recommends praziquantel for the control and treatment of schistosomiasis, with no real alternative. Pre-school children are excluded from population treatment programs mainly due to paucity of safety data on this age group.Objectives: This study investigated safety, efficacy and acceptability of praziquantel for the treatment of S. haematobium and S. mansoni infections among pre-school children aged <6years. The study also investigated the burden of schistosomiasis in this age group.Methods: Pre-school children (n=188) from Sudan were included in the study. The children were treated with praziquantel tablets at a single dose of 40 mg/kg body weight. Adverse events were assessed at 24 hours and 7 days later, via questionnaire administration to parents and guardians.Efficacy of treatment was assessed at 1, 3 and 6 months by examining stool and urine samples for schistosome eggs. Acceptability was determined by the number of children spitting or vomiting during administration of the drug.Results: The burden of schistosomiasis among pre-school children aged <6 years was high (31.1%), and this was comparable to that observed among school children-aged 6 years (32%). Praziquantel treatment achieved high cure rates (egg negative) for both S. haematobium and S.mansoni infections when assessed at 1 month after treatment (89.6-92.1%) and remained high for S. haematobium (89.6-100%) up to 6 months. However, cure rate dropped from 90.5% at one month to 58.8% and 69.2% at 3 and 6 months among S. mansoni-treated children.  Praziquantel treatment decreased egg counts considerably with  post-treatment geometric mean egg reductions rates ranging from 96.4% to 99.4% at 1 month. Acceptability of praziquantel treatment was high, only for one child the dose had to be repeated after initial spitting. Treatment resolved haematuria and improved weight of the children. There were no drug-related adverse events in all the treated children duringfollow-up at 24 hours and 7 days.Conclusions: Praziquantel is safe, effective and acceptable among children aged <6 years. Preschool children represent a high risk group for schistosomiasis and should be included in population treatment programs.Keywords:Schistosomiasis,Praziquantel, Safety,Young Children

The role of guidance in delivering cardiac resynchronization therapy:A systematic review and network meta-analysis

BACKGROUND: Positioning the left ventricular lead at the optimal myocardial segment has been proposed to improve cardiac resynchronization therapy (CRT) response. OBJECTIVES: We performed a systematic review and network meta-analysis evaluating echocardiographic and clinical response delivered with different guidance modalities compared to conventional fluoroscopic positioning. METHODS: Randomized trials with ≥6 months follow-up comparing any combination of imaging, electrical, hemodynamic, or fluoroscopic guidance were included. Imaging modalities were split whether one modality was used: cardiac magnetic resonance (CMR), speckle-tracking echocardiography (STE), single-photon emission computed tomography, cardiac computed tomography (CT), or a combination of these, defined as “multimodality imaging.” RESULTS: Twelve studies were included (n = 1864). Pair-wise meta-analysis resulted in significant odds of reduction in left ventricular end-systolic volume (LVESV) >15% (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.05–2.13, P = .025) and absolute reduction in LVESV (standardized mean difference [SMD] -0.25, 95% CI -0.43 to -0.08, P = .005) with guidance. CMR (OR 55.3, 95% CI 4.7–656.9, P = .002), electrical (OR 17.0, 95% CI 2.9–100, P = .002), multimodality imaging (OR 4.47, 95% CI 1.36–14.7, P = .014), and hemodynamic guidance (OR 1.29–28.0, P = .02) were significant in reducing LVESV >15%. Only STE demonstrated a significant reduction in absolute LVESV (SMD -0.38, 95% CI -0.68 to -0.09, P = .011]. CMR had the highest probability of improving clinical response (OR 17.9, 95% CI 5.14–62.5, P < .001). CONCLUSION: Overall, guidance improves CRT outcomes. STE and multimodality imaging provided the most reliable evidence of efficacy. Wide CIs observed for results of CMR guidance suggest more powered studies are required before a clear ranking is possible

Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

Introduction: Increased mortality has been demonstrated in older adults with coronavirus disease 2019 (COVID-19), but the effect of frailty has been unclear. Methods: This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS) and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results: Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, interquartile range [IQR] 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 versus 18–49: hazard ratio [HR] 3.57, confidence interval [CI] 2.54–5.02), frailty (CFS 8 versus 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease and cancer, but not delirium. Age, frailty (CFS 7 versus 1–3: odds ratio 7.00, CI 5.27–9.32), delirium, dementia and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusion: Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.</p